The dwarf spheroidal satellite galaxies of the Milky Way are some of the most dark-matter-dominated objects known. Due to their proximity, high dark matter content, and lack of astrophysical backgrounds, dwarf spheroidal galaxies are widely considered to be among the most promising targets for the indirect detection of dark matter via γ rays. Here we report on γ-ray observations of 25 Milky Way dwarf spheroidal satellite galaxies based on 4 years of Fermi Large Area Telescope (LAT) data. None of the dwarf galaxies are significantly detected in γ rays, and we present γ-ray flux upper limits between 500 MeV and 500 GeV. We determine the dark matter content of 18 dwarf spheroidal galaxies from stellar kinematic data and combine LAT observations of 15 dwarf galaxies to constrain the dark matter annihilation cross section. We set some of the tightest constraints to date on the annihilation of dark matter particles with masses between 2 GeV and 10 TeV into prototypical standard model channels. We find these results to be robust against systematic uncertainties in the LAT instrument performance, diffuse γ-ray background modeling, and assumed dark matter density profile. © 2014 American Physical Society.